On January 19, 2018 AVEO Oncology (NASDAQ:AVEO) reported the presentation of data from a multicenter, Phase 1b/2 study of FOTIVDA (tivozanib), a potent, selective, long half-life inhibitor of all three vascular endothelial growth factor (VEGF) receptors, in patients with advanced, unresectable hepatocellular carcinoma (HCC) (Press release, AVEO, JAN 19, 2018, View Source;p=RssLanding&cat=news&id=2327533 [SID1234523364]). The data were presented during a poster session titled, "Phase 1b/2 study of tivozanib in patients with advanced inoperable hepatocellular carcinoma" (Abstract #364) at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium held January 18-20, 2018 in San Francisco. A copy of the presentation is available at www.aveooncology.com.

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"Advanced HCC represents an area of high unmet need, with the limited number of currently available therapies often associated with increased levels of hepatotoxicity, further complicating effective treatment," said Michael Needle, MD, chief medical officer of AVEO. "Findings from this study suggest that low doses of tivozanib may yield comparable PFS and a favorable response rate to current first line standards of care for HCC patients, with a favorable safety profile which may enable therapeutic combinations with immunotherapy. We expect the clinical investigation of the combination of VEGF and checkpoint inhibition to be the next critical step forward for the treatment of HCC. We look forward to reporting preliminary Phase 2 data from the TiNivo combination trial of tivozanib and nivolumab in the lead indication of renal cell cancer at the upcoming ASCO (Free ASCO Whitepaper) GU conference, and to exploring options for pursuing similar combinations in HCC."

The study, designed to evaluate the safety and efficacy of tivozanib in advanced HCC, enrolled a total of 21 patients at three study sites. In the Phase 1b portion of the trial, which used a modified 3+3 dose escalation design, 8 patients were dosed with tivozanib starting at 1.0 mg daily for 21 days followed by 7 days off drug, with inter-patient escalation to 1.5 mg daily or de-escalation to 0.5 mg daily based on cumulative dose-limiting toxicities (DLT). Upon escalation to 1.5 mg, two patients had on target dose limiting toxicities (grade 3 mucositis and hypertension), which were likely due to the high potency of tivozanib, and came off study without completing the DLT period. Tivozanib at 1.0 mg daily was selected for the Phase 2 expansion portion and was well tolerated.

Of 19 evaluable patients, at a median follow up of 16.9 months, the study’s primary endpoint of median progression-free survival (PFS) and PFS at week 24 were 5.5 months and 47%, respectively. A partial response (PR) was seen in 4/19 patients (21%) and stable disease (SD) in 8/19 patients (42%), for a disease control rate (DCR) of 63%. Overall survival (OS) at 6 and 12 months was 58% and 25%, respectively, with a median OS of 7.5 months. Notably, 4 patients have maintained SD for over two years. There were no significant changes in HBV or HCV viral load during study treatment. Tivozanib was generally well tolerated at 1.0 mg daily, with adverse events consistent with those observed in previous tivozanib trials.

The Phase 1b/2 study was one of several studies funded by a grant provided to the National Comprehensive Cancer Network from AVEO.

About Tivozanib (FOTIVDA)

Tivozanib (FOTIVDA) is an oral, once-daily, vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) discovered by Kyowa Hakko Kirin and approved for the treatment of adult patients with advanced renal cell carcinoma in the European Union plus Norway and Iceland. It is a potent, selective and long half-life inhibitor of all three VEGF receptors and is designed to optimize VEGF blockade while minimizing off-target toxicities, potentially resulting in improved efficacy and minimal dose modifications. Tivozanib has been investigated in several tumors types, including renal cell, colorectal and breast cancers.

On January 19, 2018 Genmab A/S (Nasdaq Copenhagen: GEN) announced today that the U.S. Food and Drug Administration (FDA) has granted Priority Review to the supplemental Biologics License Application (sBLA) for the use of daratumumab (DARZALEX) in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant (ASCT) (Press release, Genmab, JAN 19, 2018, View Source [SID1234523369]). The sBLA was submitted by Genmab’s licensing partner, Janssen Biotech, Inc., in November 2017. Priority Review is an FDA designation for drugs that treat a serious condition and may provide a significant improvement in safety or efficacy. The FDA has assigned a Prescription Drug User Fee Act (PDUFA) target date of May 21, 2018 to take a decision on daratumumab in this indication. In August 2012, Genmab granted Janssen Biotech, Inc. an exclusive worldwide license to develop, manufacture and commercialize daratumumab.

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"The granting of priority review to the submission of daratumumab in front line multiple myeloma is an important step forward towards potentially bringing this product to an even larger number of patients in need," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

The sBLA submission was based on data from the Phase III ALCYONE study of daratumumab in combination with bortezomib, melphalan and prednisone in front line multiple myeloma. This data was presented as a Late-Breaking Abstract at the 2017 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and published in The New England Journal of Medicine in December, 2017.

About the ALCYONE study
This Phase III study (NCT02195479) is a randomized, open-label, multicenter study and includes 706 newly diagnosed patients with multiple myeloma who are ineligible for autologous stem cell transplantation (ASCT). Patients were randomized to receive 9 cycles of either VMP [bortezomib (a proteasome inhibitor), melphalan (an alkylating chemotherapeutic agent) and prednisone (a corticosteroid)] combined with daratumumab, or VMP alone. In the daratumumab treatment arm, patients received 16 mg/kg of daratumumab once weekly for six weeks (cycle 1; 1 cycle = 42 days), followed by once every three weeks (cycles 2-9). Following the 9 cycles, patients in the daratumumab treatment arm continued to receive 16 mg/kg of daratumumab once every four weeks until disease progression. The primary endpoint of the study is progression free survival (PFS).

About multiple myeloma
Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excess proliferation of plasma cells.1 Multiple myeloma is the third most common blood cancer in the U.S., after leukemia and lymphoma.2 Approximately 30,330 new patients were expected to be diagnosed with multiple myeloma and approximately 12,650 people were expected to die from the disease in the U.S. in 2016.3 Globally, it was estimated that 124,225 people would be diagnosed and 87,084 would die from the disease in 2015.4 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms which can include bone problems, low blood counts, calcium elevation, kidney problems or infections.5 Patients who relapse after treatment with standard therapies, including proteasome inhibitors or immunomodulatory agents, have poor prognoses and few treatment options.6

About DARZALEX (daratumumab)
DARZALEX (daratumumab) injection for intravenous infusion is indicated in the United States in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy; in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI); and as a monotherapy for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.6 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (FDA) approval to treat multiple myeloma. DARZALEX is indicated in Europe for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy and as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy. In Japan, DARZALEX is approved in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for treatment of adults with relapsed or refractory multiple myeloma. DARZALEX is the first human CD38 monoclonal antibody to reach the market. For more information, visit www.DARZALEX.com.

Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. Daratumumab triggers a person’s own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death, via apoptosis (programmed cell death).7,8,9,10,11

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. A comprehensive clinical development program for daratumumab is ongoing, including multiple Phase III studies, in relapsed and frontline multiple myeloma settings and in amyloidosis. Additional studies are ongoing or planned to assess the potential of daratumumab in other malignant and pre-malignant diseases on which CD38 is expressed, such as smoldering myeloma, NKT-cell lymphoma, myelodysplastic syndromes and solid tumors. Daratumumab has received two Breakthrough Therapy Designations from the U.S. FDA, for multiple myeloma, as both a monotherapy and in combination with other therapies.

On January 19, 2018 Rexahn Pharmaceuticals, Inc., a Delaware corporation (the "Company"), reported that clinical data from the completed Phase IIa clinical trial of RX-3117 in metastatic pancreatic cancer patients will be presented in a poster presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers (ASCO GI) 2018 annual meeting at 11:30 Pacific Time on Friday, January 19, 2018, in San Francisco, California (Press release, Rexahn, JAN 19, 2018, View Source [SID1234523375]). The poster is titled: RX-3117: Activity of an Oral Antimetabolite Nucleoside in Subjects with Pancreatic Cancer — Preliminary Results of Stage II of the Phase Ib/IIa Study

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A copy of the poster being will be available to be viewed on the Company’s website at View Source beginning at 12:00 PM Eastern Time on Friday, January 19, 2018.

On January 18, 2018 Celsion Corporation (NASDAQ:CLSN), an oncology drug development company, reported a year-end 2017 corporate review and clinical progress for two of its development programs: ThermoDox, a proprietary, heat-activated liposomal encapsulation of doxorubicin, which is in Phase III development for treatment of primary liver cancer; and GEN-1, an IL-12 DNA plasmid vector encased in a nanoparticle delivery system, which enables cell transfection followed by persistent, local secretion of the IL-12 protein, and which is in Phase I development for the localized treatment of ovarian cancer (Press release, Celsion, JAN 18, 2018, View Source [SID1234523278]).

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"In 2017, Celsion achieved our key development goals for our two lead programs, ThermoDox and GEN-1. We expect to build upon this success in 2018 as we work toward advancing our pipeline of clinical and preclinical development programs, which hold the potential to enhance the power of proven chemotherapy and immunotherapy platforms," stated Michael H. Tardugno, Celsion’s chairman, president and chief executive officer. "After successful and highly efficient financings in the second half of 2017, we have capital sufficient to complete enrollment of our Phase III OPTIMA Study and advance development through the first pre-planned efficacy analysis, which is expected in the first quarter of 2019. We further expect that our current cash position will allow us to make meaningful progress in our open-label, randomized, 86-patient Phase I/II study of GEN-1 in newly diagnosed patients with stage III and IV ovarian cancer. We are well positioned to execute on our clinical development plans to achieve meaningful milestones in the next year, and I look forward to sharing our progress."

On January 18, 2018 OncoSec Medical Incorporated ("OncoSec" or the "Company") (NASDAQ:ONCS), a company developing intratumoral cancer immunotherapies, reported preliminary clinical observations related to its pilot biomarker OMS-I140 clinical trial of ImmunoPulse IL-12 in patients with metastatic Triple Negative Breast Cancer (TNBC) (Press release, OncoSec Medical, JAN 18, 2018, View Source [SID1234523279]). The study is designed to assess whether a single cycle of ImmunoPulse IL-12 increases TNBC tumor immunogenicity by driving a pro-inflammatory cascade of events including activation of cytotoxic tumor-infiltrating lymphocytes (TILs).

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To date, five patients with TNBC have been treated with a single cycle of ImmunoPulse IL-12 (intratumoral pIL-12 [tavokinogene telseplasmid or "tavo"] with electroporation). Two of these five patients were subsequently treated with single agent nivolumab (Opdivo) – an anti-PD-1 checkpoint inhibitor treatment – as their immediate next therapy. Both of these patients, who were heavily pretreated metastatic TNBC patients with chemotherapy refractory disease, experienced robust objective responses in both ImmunoPulse IL-12 treated and untreated lesions. These clinical observations have prompted the Company to further commit to a more definitive evaluation of the combined therapies.

"Metastatic TNBC is a heterogeneous cancer with a poor prognosis where less than five percent of pre-treated patients achieve an objective response to PD-1/PD-L1 checkpoint treatments," explained Sharron Gargosky, Chief Clinical and Regulatory Officer of OncoSec. "The marked synergy shown in these patients strongly suggests that IL-12 may have primed the tumor microenvironment, impacting the clinical result. The combination of ImmunoPulse IL-12 and checkpoint inhibition represents a highly promising new therapeutic approach for TNBC and warrants a formal evaluation given the extremely low response rate in women who have failed multiple prior therapies."

Previous studies have demonstrated that breast cancer patients whose tumors are associated with markers of inflammation, such as the presence of TILs, achieve better clinical outcomes. In addition, the density of TILs is a key requirement for the anti-tumor activity of immune checkpoint inhibitors like anti-PD-1/PD-L1 antibodies. By augmenting the expansion of CD8+ tumor infilatrating T cells, ImmunoPulse IL-12 may be an ideal candidate to combine with checkpoint inhibitors, which has demonstrated low and variable activity as a monotherapy in TNBC.

Immunological examination of samples from all patients are currently being analyzed. These data, along with the full information regarding clinical observations and safety data, will be submitted for presentation at an upcoming medical meeting in 2018.

To learn more about the trial, visit www.oncosec.com. Additional details can also be found at www.clinicaltrials.gov via NCT02531425.

OPDIVO is a registered trademark of Bristol-Myers Squibb Company.

ImmunoPulse is a registered trademark of OncoSec Medical Incorporated, San Diego, CA, USA.

About Triple Negative Breast Cancer (TNBC)
Breast cancer cells that test negative for estrogen receptors (ER-), progesterone receptors (PR-), and HER2 (HER2-) means the cancer is triple negative.1 Approximately 15-20 percent of US breast cancer cases are triple negative breast cancer (TNBC),2 which disproportionately affects younger women as well as African-American women, followed by Hispanic women.3

TNBC remains a poor-prognosis breast cancer subtype, with limited treatment options for patients with advanced, recurrent disease. In the recurrent disease setting, chemotherapy remains the standard of care, and median survival is approximately 13 months from the time of disease recurrence.4 Emerging evidence shows immunotherapy options may play an important role in the treatment paradigm for TNBC. Preliminary data demonstrated the anti-PD-1 antibody, pembrolizumab, led to an objective response in approximately 18 percent of TNBC patients;5 and in the heavily pretreated population led to an objective overall response in approximately 4-8% of patients; 6 the anti-PD-L1 antibody, MPDL3280A, achieved an objective response in 33 percent of patients.7 There is increasing evidence that tumors need TILs for anti-PD-1/PD-L1 therapies to be most effective. Data also show TILs promote better responses to chemotherapy and improve clinical outcomes in breast cancer, including TNBC.8-13